Currently, there is a need for methods for delivering pharmaceutically active agents to patients in need of the active agent. One method for delivery is to encapsulate an active agent, such as, for example, a hydrophobic molecule in a polymer molecule wherein the polymer has a core that is coupled to a plurality of hydrophobic moieties.
Amphiphilic star-like macromolecules (ASMs) have been studied for drug delivery applications. (See, e.g., U.S. patent application Ser. No. 09/298,729 filed Apr. 23, 1999; U.S. patent application Ser. No. 09/422,295, filed Oct. 21, 1999, and International Patent Application US00/10050 filed Apr. 18, 2000.) The core-shell, amphiphilic structure of ASMs is covalently linked, which makes it thermodynamically stable as opposed to conventional micellar systems. Previously, aromatic cores were incorporated within the ASM structure but proved to be cytotoxic upon its degradation.
Polymeric micelles are a related type of amphiphilic block copolymers. These micelles have attracted attention as promising colloidal drug delivery systems (V. P. Torchilin J. Controlled. Release. 2001, 73, 137; C. Allen, D. et al., Colloids and Surfaces B: Biointerfaces 1999, 16, 3; and H. Otsuka, et al., Current Opinion in Colloid & Interface Science 2001, 6, 3). In these colloidal systems, the hydrophobic block typically forms the core, essentially a “microcontainer” for a lipophilic pharmaceutical (K. Kataoka, et al., Adv. Drug Delivery Rev. 2001, 47, 113). The hydrophilic part forms the outer shell, stabilizing the interface between the core and the external aqueous environment. Compared to traditional micellar systems, these polymeric surfactant-based drug carriers display apparent advantages such as lower critical micelle concentration (CMC), improved bioavailability, reduction of toxicity, enhanced permeability across the physiological barriers, and substantial changes in drug biodistribution.
Despite these advantages, the use of ASM's is somewhat limited, due to the difficulty in directing the release of the active agent at or near an appropriate target. Accordingly, there is a need for additional micellar systems and reverse micellar systems that possess some of the advantages associated with the thermodynamic stability of ASM's, but which can be used to direct active agents to specific targets.